Humoral and Cellular Immunity 6 Months After SARS-CoV-2 Infection in Solid-Organ Transplant Recipients

Purpose: The purpose of this study was to evaluate long term humoral and cellular immunity generated following SARS-CoV-2 infection in solid organ transplant recipients (SOTR). Method(s): Patients included had an active graft of an organ transplant as an adult, a positive polymerase chain reaction nasopharyngeal swab for SARS-CoV-2 after transplant, and had not received convalescent plasma, vaccination, or monoclonal antibody for SARS-CoV-2. Whole blood was obtained 6 months (+/- 1 month) after infection. Serology measured IgG and IgM titer to the SARS-CoV-2 spike protein receptor binding domain, reported as signal/ cut-off ratio (s/co). CD4+ and CD8+ T-cell reactivity was measured by Activation Induced Marker assays following stimulation of peripheral blood mononuclear cells with SARS-CoV-2 peptide pools encompassing the SARS-CoV-2 spike protein. Result(s): Of 25 subjects, 19 (76.0%) were hospitalized, 4 (16.0%) developed hypoxia, but none required mechanical ventilation. Biopsy-proven graft rejection occurred in 3 (12.0%), but none had graft loss. At 6 months, 8 (16%) had persistent symptoms and 2 (4.0%) were re-infected within one year. In the immunity study, 22 (88.0%) had reactive IgG testing and 11 (44.0%) had reactive IgM testing. Median IgG titer was 3.68 s/co (range 0.19-36.44) and IgM titer was 0.79 s/co (range 0.02-16.41). Virus-specific CD4+ T-cell reactivity was noted in 23 (92%), but only 10 (40.0%) had reactive CD8+ T-cell testing. Moderate correlation was observed between IgG and IgM titer (r=.51, p= 0.009) and between IgG titer and percent virus-specific CD4+ T-cells (r=.46, p=0.02). CD8+ T-cell reactivity was correlated with greater illness severity (p=0.043). Use of Tacrolimus, mycophenolate, or corticosteroids at time of infection was not associated with T-cell or antibody reactivity. Conclusion(s): In summary, this cohort of SOTR evaluated six months after noncritical COVID-19 illness demonstrated robust IgG and CD4+ T-cell responses, and CD8+ T-cell reactivity was correlated with higher disease severity.

Re-Infection with SARS-CoV-2 in Solid-Organ Transplant Recipients: Incidence Density and Convalescent Immunity Prior to Re-Infection

Purpose: The purpose of this study was to study our cohort of adult solid organ transplant recipients who had been infected with SARS-CoV-2 to describe the incidence density of SARS-CoV-2 re-infection, as well as the clinical features and convalescent immunity profile. Method(s): Incidence density was calculated as the total cases of re-infection divided by total days after initial diagnosis with active graft. We included those with initial infection diagnosed by polymerase chain reaction before or after transplantation, and cycle threshold values were obtained when possible. Two recipients had immunity evaluated in the weeks prior to re-infection, by measuring IgG antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools and using activation induced marker assays. Result(s): Out of 210 infected recipients, 5 (2.4%) developed re-infection, including two that had received full mRNA vaccination, but none developed hypoxia. The incidence density was 9.4 (95% confidence interval 3.9-22.6) cases/100,000 patient days. Two cases of re-infection had participated in our immunity study and had convalescent immunity data from a blood draw approximately six months after initial infection and prior to re-infection. Both mounted virus specific CD4 T cell responses prior to re-infection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). Conclusion(s): This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for re-infection even after generating reactive cellular and humoral immune responses.

Experiences in Reproductive Health Services in COVID-19 Era: A Nightmare

With consistent efforts for the last four decades in the area of family planning, it had been a rare instance to receive emergencies with uterine perforation, gut injury, septicaemia, and multiorgan failure with unsafe surgical intervention. But Coronavirus Disease 2019 (COVID-19) pandemic has caused major disruption to the family planning information and services globally. These gaps have been due to breakdown in contraceptive supply chains, closure of primary healthcare and abortion clinics, diversion of staff from family planning services to COVID-19 response team and the poor response was also due to fear of infection in hospital. As a result, many unsafe abortions in the form of near-miss mortality nightmares were revisited. The present series is of five cases, done at a tertiary care teaching hospital wherein there was mismanagement of the abortion due to lack of expert services during the COVID-19 pandemic. Uterine perforation with sepsis was observed in all the patients with bowel injury in three and broad ligament haematoma in one patient. A comprehensive, women's sexual health system response to address family planning services provision during pandemics is the need of the hour for India to avoid unwanted pregnancies and prevent additional mortality and morbidity in women.

Persistence of SARS-CoV-2-specific AB response in HIV+ individuals on art

Background: Immune dysfunction characterized by lower antibody (Ab) response to infection or vaccination has been well described among People Living with HIV (PLWH), but due to the novelty of the SARS-CoV-2 virus has not been evaluated among PLWH coinfected with SARS-CoV-2. This study compared the magnitude and longevity of Ab response to SARS-CoV-2 in a group of HIV+ and HIV-individuals infected with SARS-CoV-2 Methods: 17 HIV+COVID+ and 19 HIV-COVID+ participants were recruited from the community as part of the ACTION study and followed longitudinally at day 14, 1 month and 3 months. HIV+ were on effective ART (plasma viral load <500 copies/ml). SARS-CoV-2 infection was confirmed by SARS-COV2 DNA PCR and rapid antibody test. All participants had mild/moderate COVID-19 without hospitalization. Antibody responses (IgG and IgM) were measured using an indirect in house developed ELISA using spike RBD antigen (courtesy, Scott Boyd, Stanford University) and the data are expressed as relative Ab units based on the positive control standard. Results: The median age of HIV+ participants was 55 (26-63) with 23.5% (4/17) females. The median age for HIV-was 38 (27-78) with 57.8% (11/19) females. Time from COVID-19 diagnosis was 26 days for HIV+ and 21 for HIV-. Mean CD4 count for the HIV+ participants was 859.5 ± 287.2 cells/μl. Longitudinal analysis did not show a significant reduction in Ab response at 3 months in either HIV+ or HIV-groups. Levels of SARS-CoV-2 RBD specific IgM and IgG responses did not differ significantly between HIV+ and HIV-at any timepoint although there was a trend of lower IgM and IgG responses at 3 months in both groups compared to entry levels. Age was correlated with IgG response at day 14 (r =0.6, p = 0.02), 1 month (r =0.6, p = 0.014) and 3 month(r =0.87, p = 0.0008) in HIV+ and weakly correlated at day 14 (r =0.46, p = 0.04) in HIV-. Absolute CD4 count was not correlated with IgM and IgG responses in HIV+. Conclusion: The magnitude and persistence of Ab response to SARS-CoV-2 infection in the 3-4 months post-infection does not differ by HIV status. Although extended longitudinal follow-ups are required to gain insights about the longevity of Ab responses in HIV+ individuals, results suggest that immune protection and vaccine responses may not differ by HIV status.

Target based pharmacological approaches for drug development against novel corona virus (COVID-19)

The novel coronavirus (COVID-19) outbreak has covered almost 185 countries worldwide, causing infection to 32, 50,000 people and the death of approximately 2, 30,000 people to date. World Health Organisation (WHO) has declared it a pandemic that seems to be unstoppable as no vaccine or drug is available as of now to kill the virus. Several research labs are trying to develop a vaccine against the virus as soon as possible. Several drugs, like a combination of hydroxychloroquine and azithromycin, have been shown to be beneficial in COVID-19 infected patients. In-silico experiments suggest that methylcobalamin and valproic acid can reduce virus titer and thereby reducing the severity of the infection. BCG vaccine may provide immunity against the infection of coronavirus. As there is a strong correlation between the immune system of the infected person and the virulence of coronavirus, any therapy which could help in boosting the immune system shall be of prime importance. Hence, the efficacy of convalescent plasma therapy has been tried in COVID-19 infection, thinking that the antibodies from convalescent plasma might suppress viremia. Angiotensin-converting enzyme 2 (ACE2) receptors have been shown to be the entry point in human cells for COVID-19. RNA dependent RNA polymerase (RdRp) of the virus could be a potent target for inhibitor drug design and discovery against COVID-19. Recently, non-classical actions of vitamin D have been recognized. It affects upon cell proliferation and differentiation as well as immunologic functions resulting in an ability to maintain tolerance and to promote protective immunity. Zinc has been shown to affect multiple aspects of the immune system. Zinc has a significant role in the normal development and function of cells mediating innate immunity, neutrophils, and natural killer (NK) cells. The deficiency of zinc affects macrophages, phagocytosis, cytokine production, and intracellular killing. As there is a strong correlation between the immune system of the infected person and the virulence of coronavirus, any therapy which could help in boosting the immune system shall be of prime importance.